Ginsenoside Rg3 Upregulates Myotube Formation and Mitochondrial Function, Thereby Protecting Myotube Atrophy Induced by Tumor Necrosis Factor-Alpha
Abstract
Ethnopharmacological relevance Ginsenoside Rg3 from Panax ginseng has reported to have multiple pharmacological activities including anti-diabetics, anti-inflammation and anti-cancer. However, the effect of ginsenoside Rg3 on myogenic differentiation and muscle atrophy is unknown.Aim to the study In this study, we investigated the myogenic effect and underlying molecular mechanisms of ginsenoside Rg3 on myotube atrophy induced by tumor necrosis factor-α (TNF-α).Materials and methods C2C12 myoblasts were induced to differentiate for one day followed by the treatment of TNF-α along with vehicle or ginsenoside Rg3 for additional 2 days and subjected to immunoblotting, immunocytochemistry, quantitative RT-PCR and biochemical analysis for mitochondrial function.Results Ginsenoside Rg3 promotes myogenic differentiation and multinucleated myotube formation through Akt activation in a dose-dependent manner, without any cytotoxicity. Ginsenoside Rg3 treatment restores myotube formation and increases myotube diameters under TNF-α-treated conditions. Ginsenoside Rg3 enhances Akt/mTOR (mammalian target of rapamycin) signaling that in turn stimulates muscle-specific gene expression such as myosin heavy chain (MHC) and Myogenin, and suppresses the expression of muscle-specific ubiquitin ligases. In addition, ginsenoside Rg3 in TNF-α-treated myotubes significantly inhibits the production of mitochondrial ROS and restores mitochondrial membrane potential (MMP) and ATP contents. Furthermore, ginsenoside Rg3 upregulates the activities and expression of peroxisome proliferator-activated receptor-γ coactivator-1α (PGC1α) and the mitochondrial biogenetic transcription factors, nuclear respiratory factor-1 (NRF1) and mitochondrial transcription factor A (Tfam) in TNF-α-induced myotube atrophy.Conclusions This study provides a mechanistic insight into the effect of ginsenoside Rg3 on myogenic differentiation and myotube atrophy, suggesting that ginsenoside Rg3 has a promising potential as a therapeutic or neutraceutical remedy to intervene muscle weakness and atrophy.
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Ginsenoside Rg3 enhances myotube growth and suppresses the expression of MuRF1 and MAFbx in TNF-α-induced muscle atrophy of C2C12 myotubes via the activation of Akt/mTOR signaling pathway.
“Like ginsenoside Rg1, ginsenoside Rg3 enhances myotube growth and suppresses the expression of MuRF1, MAFbx in TNF-α-induced muscle atrophy of C2C12 myotubes via the activation of Akt/mTOR signaling pathway.”
From Nutraceuticals in the Prevention and Treatment of the Muscle Atrophy (2021) · cites this paper as [149]
Ginsenoside Rg3 enhances mitochondrial functions and upregulates the expression of PGC1α, Nrf1, and Tfam, and thereby protects TNF-α-induced myotube atrophy in C2C12 cells.
“Furthermore, ginsenoside Rg3 enhances mitochondrial functions and upregulates the expression of PGC1α, Nrf1, and Tfam, and thereby protects TNF-α-induced myotube atrophy in C2C12 cells [149].”
From Nutraceuticals in the Prevention and Treatment of the Muscle Atrophy (2021) · cites this paper as [149]
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Nutraceuticals in the Prevention and Treatment of the Muscle Atrophy
Wang, Y., Liu, Q., Quan, H., Kang, S.-G., Huang, K., & Tong, T. (2021) · Nutrients · doi:10.3390/nu13061914 · Cited by 61 · see citing works
Seok, Y. M., Yoo, J.-M., Nam, Y., Kim, J., Kim, J. S., Son, J.-H., & Kim, H. J. (2021) · Journal of Ethnopharmacology · doi:10.1016/j.jep.2020.113557 · Cited by 27 · see citing works
- Authors
- Lee, S.-J., Bae, J. H., Lee, H., Lee, H., Park, J., Kang, J.-S., & Bae, G.-U.
- Affiliations
- Sookmyung Women's University (KR)
- Sungkyunkwan University (KR)
- Chungnam National University (KR)
- Corresponding author
- Bae, Gyu-Un
- Venue
- Journal of Ethnopharmacology
- Publisher
- Elsevier BV
- Published
- 2019-10
- Volume
- 242
- Pages
- 112054
- ISSN
- 0378-8741 (ISSN-L)
- OpenAlex
- W2954460301
- Cited by
- 38
- References
- 49
- Citations by year
- 2026: 3 · 2025: 6 · 2024: 2 · 2023: 8 · 2022: 8 · 2021: 6 · 2020: 5
- FWCI
- 1.57
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Ethnopharmacology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Industrial Core Technology Development Program (10063475)
- MOTIE
- NRF (2017R1D1A1B03032839)
- MSIP
- Research Institute
- Green Cross Wellbeing Co., Ltd.
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ginseng Biological Effects and Applications
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Muscle Physiology and Disorders
- Health Sciences › Medicine › Physiology › Adipose Tissue and Metabolism
- Keywords
- ginsenoside Rg3, Panax ginseng, myotube atrophy, TNF-α, myogenesis, Akt/mTOR signaling, mitochondrial function, mitochondrial reactive oxygen species, PGC-1α, NRF1, TFAM, muscle atrophy, myosin heavy chain, myogenin, ubiquitin ligase, muscle weakness
- MeSH terms
- Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha, Animals, Cell Differentiation, Cell Line, Mitochondria, Muscle, Muscular Atrophy, Tumor Necrosis Factor-alpha, Reactive Oxygen Species, Muscle Fibers, Skeletal, Ginsenosides, Proto-Oncogene Proteins c-akt, Mice, Membrane Potential, Mitochondrial
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